Metal ions are necessary for activating the sugar binding function of certain lectins. Concanavalin A (Con A) and a lima bean lectin (LBL) are two examples. Con A is by far the most extensively studied of all the lectins. This research is directed toward elucidating the role played by metal ions in determining the protein activity. Con A, according to most published research, requires a transition metal ion and a calcium ion for preparation of the sugar binding site. Metal ion binding to Con A is being studied by electron spin resonance and water proton relaxation. Manganese ion binding is cooperative in the presence of calcium ions. The cooperativity in Mn2 ion binding is reflected in the kinetic study. We have shown that in opposition to the currently accepted dogma, Ca2 ion can bind at pH 7.0 when no transition metal is present. We are now examining the ability of Con A to bind sugar when only Ca2 ion is present to activate the protein. Binding of sugar to Con A is also being examined by calorimetric methods. Enthalpies are directly measured and the free energies and entropies can be calculated. The work is now being extended to the study of LBL. The metal ion requirements and its effect on protein structure and sugar binding activity are being studied by methods applied to investigation of Con A.